SUMMARY: Novel predictors of survival among breast cancer patients with/without HIV in South Africa As antiretroviral therapy (ART) improves survival among HIV-infected individuals, they become susceptible to diseases of middle and older ages, including epithelial cancers. In sub-Saharan Africa, where HIV prevalence approaches 20%, breast cancer has become the most common malignancy and cause of cancer-related death among women. Few studies have addressed the effects of HIV infection and ART on the clinical presentation, treatment, and prognosis of breast cancer. We propose to continue our study of those effects among South African women. In our prior work, we investigated demographic and clinical characteristics of 1200 breast cancer patients (18% HIV+), diagnosed 2007-2012 at the Chris Hani Baragwanath Academic Hospital Breast Clinic in Soweto, Johannesburg. Since 2015, for our R01-funded (CA192627) South African Breast Cancer and HIV Outcomes (SABCHO) study, we recruited and followed women with breast cancer newly diagnosed at 5 hospital centers in Johannesburg and KwaZulu Natal, to investigate the effects of HIV and ART on breast cancer treatment and outcomes. This collaboration of University of the Witwatersrand (Wits) and Columbia University Medical Center (CUMC) has yielded 16 publications to date (Wits contact PI and PD are former CUMC D43 trainees). We now propose: 1) to analyze determinants of mortality among the >3,000 women enrolled in the SABCHO study (21% HIV+), of whom 28.5% of HIV+ and 20.8% of HIV- patients have already died. We will assess cancer treatments, comorbidities, viral load control, clinical and sociodemographic mediators of the effects of HIV on mortality; 2) to examine the associations between sarcopenia , chemotherapy dose reductions and grade 3/4 toxicities, and early mortality among 600 black women (150 HIV+, 450 HIV-) newly diagnosed with BC; 3) to compare in HIV+ and HIV- patients, self-reported tamoxifen adherence and tolerance, plasma levels of tamoxifen and its metabolites, and factors that may affect these levels: treatment adherence, enzyme inhibition- and induction-based drug interactions, and genetic polymorphisms in enzymes involved in tamoxifen metabolism and pharmacokinetics; and 4) to train a) Sefako Makgatho University investigators in epidemiologic research, research ethics, contracts, grant budgeting and management, informed consent, survey research, and blood specimen logistical management; and b) masters students from Zimbabwe in pharmacogenomics and drug-drug interactions pertinent to breast cancer patients receiving ART and other chronic comorbidity treatments.